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Yorodumi- EMDB-18268: P301S Tau Filaments from the Brains of PS19 Transgenic Mouse Line -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18268 | |||||||||
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Title | P301S Tau Filaments from the Brains of PS19 Transgenic Mouse Line | |||||||||
Map data | ||||||||||
Sample |
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Keywords | P301S tau / Frontotemporal dementia and parkinsonism linked to chromosome 17 / Transgenic mice / Electron cryo-microscopy / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / axon development / intracellular distribution of mitochondria / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / axolemma / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / positive regulation of protein localization / regulation of cellular response to heat / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / protein-folding chaperone binding / single-stranded DNA binding / actin binding / cellular response to heat / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / sequence-specific DNA binding / amyloid fibril formation / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.05 Å | |||||||||
Authors | Schweighauser M / Murzin AG / Macdonald J / Lavenir I / Crowther RA / Scheres SHW / Goedert M | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Acta Neuropathol Commun / Year: 2023 Title: Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau. Authors: Manuel Schweighauser / Alexey G Murzin / Jennifer Macdonald / Isabelle Lavenir / R Anthony Crowther / Sjors H W Scheres / Michel Goedert / Abstract: Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. ...Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the brains of Tg2541 and PS19 mice. Both lines express human P301S tau (0N4R for Tg2541 and 1N4R for PS19) on mixed genetic backgrounds and downstream of different promoters (murine Thy1 for Tg2541 and murine Prnp for PS19). The structures of tau filaments from Tg2541 and PS19 mice differ from each other and those of wild-type tau filaments from human brains. The structures of tau filaments from the brains of humans with mutations P301L, P301S or P301T in MAPT are not known. Filaments from the brains of Tg2541 and PS19 mice share a substructure at the junction of repeats 2 and 3, which comprises residues I297-V312 of tau and includes the P301S mutation. The filament core from the brainstem of Tg2541 mice consists of residues K274-H329 of tau and two disconnected protein densities. Two non-proteinaceous densities are also in evidence. The filament core from the cerebral cortex of line PS19 extends from residues G271-P364 of tau. One strong non-proteinaceous density is also present. Unlike the tau filaments from human brains, the sequences following repeat 4 are missing from the cores of tau filaments from the brains of Tg2541 and PS19 mice. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18268.map.gz | 77.2 MB | EMDB map data format | |
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Header (meta data) | emd-18268-v30.xml emd-18268.xml | 15.2 KB 15.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18268_fsc.xml | 15.6 KB | Display | FSC data file |
Images | emd_18268.png | 25.7 KB | ||
Masks | emd_18268_msk_1.map | 325 MB | Mask map | |
Filedesc metadata | emd-18268.cif.gz | 5.4 KB | ||
Others | emd_18268_half_map_1.map.gz emd_18268_half_map_2.map.gz | 259.4 MB 259.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18268 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18268 | HTTPS FTP |
-Validation report
Summary document | emd_18268_validation.pdf.gz | 963.4 KB | Display | EMDB validaton report |
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Full document | emd_18268_full_validation.pdf.gz | 963 KB | Display | |
Data in XML | emd_18268_validation.xml.gz | 23.4 KB | Display | |
Data in CIF | emd_18268_validation.cif.gz | 30.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18268 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18268 | HTTPS FTP |
-Related structure data
Related structure data | 8q92MC 8q96C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18268.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_18268_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_18268_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_18268_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : P301S Tau Protein Filament (PS19)
Entire | Name: P301S Tau Protein Filament (PS19) |
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Components |
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-Supramolecule #1: P301S Tau Protein Filament (PS19)
Supramolecule | Name: P301S Tau Protein Filament (PS19) / type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all Details: Human P301S tau filaments extracted from the brains of transgenic mouse line PS19 |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: PS19 / Organ: Brain / Tissue: Cerebral Cortex |
-Macromolecule #1: Microtubule-associated protein tau
Macromolecule | Name: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) / Strain: Transgenic PS19 / Organ: Brain / Tissue: Cerebral Cortex |
Molecular weight | Theoretical: 9.96743 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: GGGKVQIINK KLDLSNVQSK CGSKDNIKHV SGGGSVQIVY KPVDLSKVTS KCGSLGNIHH KPGGGQVEVK SEKLDFKDRV QSKIGSLDN ITHVP UniProtKB: Microtubule-associated protein tau |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 96000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |